Pregnancy and live birth following the transfer of vitrified–warmed blastocysts derived from zona- and corona-cell-free oocytes

Abstract

This study reports two clinical pregnancies and one live birth following the transfer of vitrified blastocysts developed from oocytes with neither zona pellucida nor corona cells. Two zona-free oocytes obtained from two patients of advanced maternal age undergoing minimal stimulation were normally fertilized after intracytoplasmic sperm injection. In case 1, all four blastomeres of the zona-free embryo were loosely associated and inserted back into ruptured zona on day 2. Zona-free embryo from case 2 had tight contacts between blastomeres and was cultured without zona. Both embryos derived from zona-free oocytes progressed to blastocyst stage and were cryopreserved by vitrification. When patients came back for a cryopreserved embryo transfer, both vitrified blastocysts survived warming. In case 1, transfer of a warmed blastocyst with reconstructed zona resulted in a clinical pregnancy that ended in a spontaneous abortion at 22 weeks. In case 2, live birth was achieved with a normal healthy baby (male) weighing 2381 g at 40 weeks' gestation. This report emphasizes the importance of maintenance of normal cell arrangement on the subsequent embryonic development for a zona-free oocyte. Zona-free oocytes may provide a valuable source of embryos for infertility patients, especially for those with a limited number of oocytes.

ZP4 confers structural properties to the zona pellucida essential for embryo development

“…ZP plays an essential protective role during preimplantation embryo development, as despite the exception of a single case report where zona-free embryos were developed in vitro up to blastocyst before transfer (Shu et al, 2010), zona denuded embryos have been largely considered unable to complete in vivo development (Bronson and McLAREN, 1970; Modliński, 1970). This protective function was severely impaired following ZP4 ablation, ultimately causing embryonic death and infertility.…”

Live birth in a complete zona-free patient: a case report

“…The complete absence of ZP in oocytes is a rare event in IVF treatment; however, oocytes with damaged or partially absent zona due to laboratory manipulations are not uncommon [1,5,7,13]. Consequently, much of the published experiences of ZP-free patients are cases of ZP damage and loss during handling, rather than a complete absence due to ZP production failure.…”

Infertility and Immunocontraception based on zona pellucida

“…Therefore, in humans, aberrant expression of ZP proteins by genetic ZP mutations might cause infertility. Case reports described that ZP-free or ZP-fragile oocytes were retrieved from women with recurrent GEFS [53,54]. Such ZP abnormalities might arise from mutations in the genes encoding ZP proteins, although careful investigation is needed for definitive diagnosis.…”